Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and Rhinoconjunctivitis.

OBJECTIVES: Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is diagnosed in at least one-third of patients with suspected eosinophilic esophagitis (EoE). We aimed to evaluate the durability and factors influencing long-term efficacy of PPI therapy. METHODS: Retrospective multicenter cohort study of patients with PPI-REE who had at least 12 months of follow-up. PPI therapy was tapered to the lowest dose, which maintained clinical remission. Primary outcomes were the proportion of patients with loss of histological response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms were determined from blood samples in a subset of patients. RESULTS: Seventy-five PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty-five (73%) had sustained histological remission on low-dose PPI therapy. Loss of response was significantly higher in those patients with a CYP2C19 rapid metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs. 13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of loss of response. Among relapsing patients, eosinophilia was limited to the distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia, all showing a CYP2C19 rapid metabolizer genotype, regained histological remission after PPI dose intensification. CONCLUSIONS: Most PPI-REE patients remain in long-term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and rhinoconjunctivitis were independent predictors of loss of response to PPI, but patients frequently responded to PPI dose escalation.

Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance.

BACKGROUND & AIMS: Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents. METHODS: We performed a prospective noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned randomly to groups given hybrid therapy (40 mg omeprazole and 1 g amoxicillin, twice daily for 14 days; 500 mg clarithromycin and 500 mg nitroimidazole were added, twice daily for the final 7 days) or concomitant therapy (same 4 drugs taken concurrently, twice daily for 14 days). We assessed bacterial resistance to these drugs in a subset of patients using the E-test. Efficacy, side effects, and compliance were determined. RESULTS: In per-protocol analysis, rates of eradication for hybrid and concomitant therapies were 92% (95% confidence interval [CI], 87%-95%) and 96.1% (95% CI, 93%-99%), respectively (P = .07). In intention-to-treat analysis, rates were 90% (95% CI, 86%-93%) and 91.7% (95% CI, 87%-95%), respectively (P = .35). Almost all patients (95.5%) were fully compliant; 23.5% of patients had H pylori strains that were resistant to clarithromycin (Italy, 26%; Spain, 19.5%), 33% were resistant to metronidazole (Italy, 33%; Spain, 34%), and 8.8% were resistant to both drugs (Italy, 7.1%; Spain, 11.5%). Side effects (only mild) were reported in 51.5% of patients (47% hybrid vs 56% concomitant; P = .06). Compliance greater than 80% was the only significant predictor of eradication (odds ratio, 12.5; 95% CI, 3.1-52; P = .001). Significantly more patients were compliant with hybrid therapy (98.8%) than concomitant therapy (95.2%; P = .05). CONCLUSIONS: Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance. ClinicalTrials.gov number NCT01464060.

Preparación con picosulfato sódico/citrato de magnesio en dosis fraccionadas para colonoscopias en turno de mañana realizadas entre las 2 y 6 horas posteriores a la ingesta de líquidos / Split-dose sodium picosulphate/magnesium citrate for morning colonoscopies performed 2 to 6hours after fluid intake

Introducción La preparación de la colonoscopia en dosis fraccionadas (DF) mejora la calidad de la limpieza. Objetivo Comparar la preparación para colonoscopias de mañana con picosulfato sódico/citrato de magnesio (Citrafleet®) en DF con su administración el día previo. Material y métodos Pacientes consecutivos fueron aleatorizados a Citrafleet® el día anterior o en DF administrándose la segunda mitad individualizadamente con un intervalo de 2 a 6 h antes del procedimiento, sin bisacodilo. La sedación fue realizada con propofol, definiéndose una limpieza adecuada si ≥ 6 (escala de Boston), sin ninguna puntuación 0/1.ResultadosSe incluyeron 193 pacientes. La calidad de la limpieza fue significativamente mejor en el grupo DF de manera global (7 vs. 5,2, p<0,001), en ciego (2,4 vs. 1,4, p<0,001), colon ascendente (2,5 vs.1,6, p = 0,001) y colon transverso (2,4 vs. 2, p = 0,004). La limpieza adecuada del colon se detectó en un porcentaje significativamente superior de pacientes con DF (71 vs. 30%, p<0,001). Los pacientes del grupo DF bebieron un volumen de líquido superior (4,9 vs. 4 l, p = 0,006) y percibieron con mayor frecuencia el proceso como fácil o muy fácil de completar (89 vs. 68%, p = 0,04), aunque durmieron menor número de horas (6,5 vs.7,9, p<0,001). No se registró ninguna bronconeumonía aspirativa. Conclusiones La preparación en DF con Citrafleet® incrementó en un 40% las exploraciones con una limpieza adecuada, especialmente en colon proximal, aumentó el volumen de ingesta líquida y mejoró la percepción de facilidad para su cumplimiento, sin complicaciones derivadas de la sedación (AU)

Background Split dosage of bowel preparations has been shown to substantially improve bowel cleansing. Aim To compare the split dose (SD) sodium picosulphate/magnesium oxide/anhydrous citric acid (Citrafleet®) regimen for morning colonoscopies with standard cleansing the day before. Methods Consecutive outpatients were randomized to receive Citrafleet® the day before colonoscopy or SD, in whom the second half was administered on an individual basis from 2 to 6hours before the procedure. No bisacodyl was administered. All procedures were performed with non-anesthesiologist administered propofol sedation. The Boston scale was used to assess the quality of bowel preparation (adequate cleansing if score ≥ 6, with no score of 0/1 in any segment).Results A total of 193 patients were included. Overall bowel cleansing was significantly better in the SD group (7 vs. 5.2, p<0.001), as well as in the cecum (2.4 vs. 1.4, p < 0.001), ascending colon (2.5vs. 1.6, p<0.001) and transverse colon (2.4 vs. 2, p = 0.004). A significant proportion of SD patients had adequate bowel cleansing (71% vs. 30%, p<0.001). Patients in the SD group drank a greater amount of liquid (4.9 vs. 4 liters, p = 0.006) and more frequently perceived the cleansing process to be easy or very easy to complete (89 vs. 68%, p = 0.04), although they slept significantly fewer hours (6.5 vs. 7.9, p<0.001). No bronchoaspiration pneumonia was reported. Conclusions SD Citrafleet® 2 to 6hours before colonoscopy increased the rate of procedures with adequate bowel cleansing by 40%, especially in the proximal colon, allowed more liquids to be drunk and increased the perception of ease in completing the preparation, with no sedation-related complications (AU)

[Split-dose sodium picosulphate/magnesium citrate for morning colonoscopies performed 2 to 6 hours after fluid intake]. / Preparación con picosulfato sódico/citrato de magnesio en dosis fraccionadas para colonoscopias en turno de mañana realizadas entre las 2 y 6 horas posteriores a la ingesta de líquidos.

BACKGROUND: Split dosage of bowel preparations has been shown to substantially improve bowel cleansing. AIM: To compare the split dose (SD) sodium picosulphate/magnesium oxide/anhydrous citric acid (Citrafleet(®)) regimen for morning colonoscopies with standard cleansing the day before. METHODS: Consecutive outpatients were randomized to receive Citrafleet(®) the day before colonoscopy or SD, in whom the second half was administered on an individual basis from 2 to 6 hours before the procedure. No bisacodyl was administered. All procedures were performed with non-anesthesiologist administered propofol sedation. The Boston scale was used to assess the quality of bowel preparation (adequate cleansing if score ≥ 6, with no score of 0/1 in any segment). RESULTS: A total of 193 patients were included. Overall bowel cleansing was significantly better in the SD group (7 vs. 5.2, p<0.001), as well as in the cecum (2.4 vs. 1.4, p < 0.001), ascending colon (2.5 vs. 1.6, p<0.001) and transverse colon (2.4 vs. 2, p=0.004). A significant proportion of SD patients had adequate bowel cleansing (71% vs. 30%, p<0.001). Patients in the SD group drank a greater amount of liquid (4.9 vs. 4 liters, p=0.006) and more frequently perceived the cleansing process to be easy or very easy to complete (89 vs. 68%, p=0.04), although they slept significantly fewer hours (6.5 vs. 7.9, p<0.001). No bronchoaspiration pneumonia was reported. CONCLUSIONS: SD Citrafleet(®) 2 to 6 hours before colonoscopy increased the rate of procedures with adequate bowel cleansing by 40%, especially in the proximal colon, allowed more liquids to be drunk and increased the perception of ease in completing the preparation, with no sedation-related complications.

Talidomida en dosis altas para la hemorragia digestiva oscura grave idiopática en una paciente de alto riesgo trombótico / High-dose thalidomide for severe idiopathic obscure gastrointestinal bleeding in a patient at high-thrombotic risk

Se presenta el caso de una mujer de 81 años con accidentes vasculares cerebrales (ACV) recurrentes con doble antiagregación y hemorragia digestiva de origen oscuro. No se encontró el origen del sangrado con cápsula endoscópica, enteroscopia de doble balón, laparotomía exploradora y enteroscopia intraoperatoria bidireccional desde boca a ano. La paciente requirió la transfusión de 117 concentrados de hematíes durante 2 años pese a suspensión de la medicación antiagregante y tratamiento con análogos de la somatostatina. Por ello, se inició terapia con dosis crecientes de talidomida, hasta 300mg, asociadas a profilaxis tromboembólica durante 3 meses, sin respuesta. Al suspender la heparina, la hemorragia se controló durante 3 meses, pero se retiró la talidomida por efectos secundarios. Dado que la hemorragia recidivó al mes de la suspensión, se realizó un segundo ciclo de 3 meses de tratamiento con talidomida. Durante un año de seguimiento, la paciente no ha precisado transfusión de hemoderivados (AU)

We report the challenging case of an 81-year-old woman on dual antiplatelet therapy with recurrent strokes, who presented with severe obscure gastrointestinal bleeding. A thorough diagnostic work-up, including capsule endoscopy, double balloon enteroscopy, arteriography, exploratory laparotomy and mouth-to-anus intraoperative enteroscopy, failed to reveal the source of the bleeding. During a 2-year period, the patient required 117 packed red blood cell units, despite withdrawal of antiplatelet drugs and empirical therapy with high-dose somatostatin analogues. The patient was administered an increasing dosage of thalidomide, up to 300mg/day, with thromboembolism prophylaxis for 3 months, with no clinical response. The bleeding stopped for 3 months after heparin was discontinued, but thalidomide had to be withdrawn owing to adverse effects. Since bleeding recurred a month later, the patient underwent another 3-month course of thalidomide. The patient has not required further blood transfusion after a 1-year follow-up (AU)

[High-dose thalidomide for severe idiopathic obscure gastrointestinal bleeding in a patient at high-thrombotic risk]. / Talidomida en dosis altas para la hemorragia digestiva oscura grave idiopática en una paciente de alto riesgo trombótico.

We report the challenging case of an 81-year-old woman on dual antiplatelet therapy with recurrent strokes, who presented with severe obscure gastrointestinal bleeding. A thorough diagnostic work-up, including capsule endoscopy, double balloon enteroscopy, arteriography, exploratory laparotomy and mouth-to-anus intraoperative enteroscopy, failed to reveal the source of the bleeding. During a 2-year period, the patient required 117 packed red blood cell units, despite withdrawal of antiplatelet drugs and empirical therapy with high-dose somatostatin analogues. The patient was administered an increasing dosage of thalidomide, up to 300 mg/day, with thromboembolism prophylaxis for 3 months, with no clinical response. The bleeding stopped for 3 months after heparin was discontinued, but thalidomide had to be withdrawn owing to adverse effects. Since bleeding recurred a month later, the patient underwent another 3-month course of thalidomide. The patient has not required further blood transfusion after a 1-year follow-up.